Episode Initiation Research Articles

Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents

Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents. To assess the association between antihypertensive medication initiation and risk of fracture. This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023. Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy. The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching. Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score-matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]). Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

Initiation Patterns of Disease-Modifying Therapies for Multiple Sclerosis Among US Adults and Children, 2001 Through 2020

Many disease-modifying therapies (DMTs) have been approved for multiple sclerosis (MS) in the past 2 decades. Research evaluating how these approvals have changed real-world prescribing patterns is scarce. To evaluate patterns in DMT initiations between 2001 and 2020 among commercially insured US adults and children with MS. This serial cross-sectional study was conducted from 2001 through 2020 (mean patient enrollment duration, 4.8 years) and used US commercial claims data (MarketScan). Analysis took place between January 2022 and March 2023. Of 287 084 patients with MS identified, 113 583 patients (113 095 adults and 488 children) with MS newly initiated at least 1 DMT. New initiation episode of a DMT, defined as no claim for the same DMT in the previous year. The proportion of total DMT initiations per year attributable to each DMT. Trends in initiations were evaluated annually. The study team identified 153 846 DMT initiation episodes among adults (median age, 46 [IQR, 38-53) years]; 86 133 female [76.2%]) and 583 among children (median age, 16 (IQR, 14-17) years; 346 female [70.9%]). Among adults, use of platform injectables showed an absolute decline of 73.8% over the study period, driven by a 61.2% reduction in interferon β initiations (P < .001 for trend). In contrast, the 2010 introduction of oral DMTs led to a rise in their use from 1.1% (2010) to 62.3% (2020) of all DMT initiations (P = .002 for trend). Infusion therapy initiations remained relatively low, accounting for 3.2% of all initiations since their introduction in 2004 but increased modestly annually after ocrelizumab was introduced (2017), reaching 8.2% of all initiations in 2020 (P < .001 for trend). Children showed similar initiation patterns, except for preferred oral therapy. Between 2019 and 2020, dimethyl fumarate was the most commonly initiated DMT in adults (23.3% to 27.2% of all initiations), while in children fingolimod was the most commonly initiated (34.8% to 68.8%). Current MS treatment guidelines emphasize shared decision-making between patients and clinicians to balance treatment efficacy, safety, cost, and convenience. This study found that oral DMTs were the predominant DMT type initiated by 2020. The cause of this shift cannot be determined from this study, but may reflect several factors, including convenience of administration, direct-to-consumer advertising, or insurance restrictions.

Mesoscale Moisture Transport in Determining the Location of Daytime Convection Initiations Clustered in Time and Space Over Southern China

AbstractConvective initiation (CI) episodes are defined as a series of CIs that occur in clusters in time and space, and their prediction remains a challenge due to their complex mechanisms. In the present study, high‐resolution convection‐permitting simulations and observations were conducted to investigate the source of inhomogeneous instability for a cluster of daytime CIs gathering in a northeast‐southwest oriented region in South China where the convergence boundary for lifting was not evident. In the region of the CI episode, low‐level water vapor was enhanced significantly, which thus induced the heterogeneity of convective available potential energy. The enhanced moisture and instability in the CI episode region were caused by a mesoscale anticyclonic moisture channel. Mesoscale moisture transport formed under both the inertial oscillation of ageostrophic winds and the mesoscale high‐pressure disturbances in the daytime. The revealed mechanism is further confirmed by sensitivity experiments, where mesoscale anticyclonic transport is highly sensitive. Water vapor transport was affected by the evolution of mesoscale pressure disturbances and dominated the location and shape of the CI episode. Stronger mesoscale pressure disturbances resulted in the subsequent mesoscale anticyclonic airflow coming from various high‐pressure systems and conveying moisture farther east, and therefore, a CI episode occurred farther east by dozens to hundreds of kilometers. The climatology of the daytime CI episode also showed that the various mesoscale moisture transports confined moisture within the CI episode regions under weak convergence.

PDB107 ASSESSING ASYMMETRICAL PRESCRIBING OF ANTIDIABETIC DRUGS RELATIVE TO DIAGNOSIS OF NAFLD

No drugs have yet been FDA- approved to treat non- alcoholic fatty liver disease (NAFLD). Several clinical trials have demonstrated beneficial effects of antidiabetic drugs (i.e., pioglitazone, liraglutide, and exenatide) in treating NAFLD. However, whether diagnosis of NAFLD influences clinicians’ choice of antidiabetic agents is unknown. This study assessed the initiation timing of glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and thiazolidinediones (TZDs) relative to a NAFLD diagnosis. We conducted a retrospective cohort study from 2012- 2019 using MarketScan® Explorys® Claims-EMR Data Set. Adult patients with diagnosis of NAFLD who newly initiated GLP- 1RAs, DPP- 4is, or TZDs were selected from the database. The index date was defined as the initiation date of an antidiabetic agent. NAFLD was identified using the earliest date of diagnosis 365 days before and after the index date. We described the raw frequency distribution of antidiabetic drugs initiation relative to a NAFLD diagnosis. Overall, 4,640 patients with diagnosis of NAFLD contributed 5,180 initiation episodes (nGLP- 1RAs = 2,243, nDPP- 4is = 2,587, nTZDs = 350). Approximately 60% of the initiations were subsequent to the diagnosis of NAFLD. Among GLP1- RAs, DPP-4is, and TZDs, the distribution of dispensed products was similar before and after the NAFLD diagnosis, with a slight decline in sitagliptin (40.3% prior to NAFLD vs 36.9% after NAFLD) and increase in dulaglutide (10.2% prior to NAFLD vs 12.5% after NAFLD) and linagliptin (7.0% prior to NAFLD vs 8.3% after NAFLD). The preliminary findings from this study suggest that patients are more likely to initiate these GLP-1RAs, DPP-4is, and TZDs after a NAFLD diagnosis. Further analysis will aim to establish the direct effect of a NAFLD diagnosis on the initiation of these drugs.

Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study

Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice. CVD-REAL 3 was a multinational observational cohort study in which new users of SGLT2 inhibitors and other glucose-lowering drugs with measurements of estimated glomerular filtration rate (eGFR) before and after (within 180 days) initiation were identified via claims, medical records, and national registries in Israel, Italy, Japan, Taiwan, and the UK. Propensity scores for SGLT2 inhibitor initiation were developed in each country, with 1:1 matching with initiators of other glucose-lowering drugs. Propensity score included (in addition to other clinical and demographic variables) baseline eGFR and eGFR slope before SGLT2 inhibitor or other glucose-lowering drug initiation. The main outcome measure was rate of eGFR decline (slope) calculated with a linear mixed regression model. Differences in eGFR slope between SGLT2 inhibitors and other glucose-lowering drugs were calculated and pooled. We also assessed a composite outcome of 50% eGFR decline or end-stage kidney disease. After propensity matching, there were 35 561 episodes of treatment initiation in each group, from 65 231 individual patients. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin accounted for 57·9%, 34·1%, 5·7%, 1·4%, 0·5%, and 0·4% of SGLT2 inhibitor initiation episodes, respectively. At baseline, 29 363 (41·3%) of 71 122 initiations were in women, mean age was 61·3 years, mean HbA1c was 72 mmol/mol (8·71%), and mean eGFR was 90·7 mL/min per 1·73 m2. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other glucose-lowering drugs 1·53 mL/min per 1·73 m2 per year, 95% CI 1·34-1·72, p<0·0001). During a mean follow-up of 14·9 months, 351 composite kidney outcomes occurred: 114 (3·0 events per 10 000 patient-years) among initiators of SGLT2 inhibitors and 237 (6·3 events per 10 000 patient-years) among initiators of other glucose-lowering drugs (hazard ratio 0·49, 95% CI 0·35-0·67; p<0·0001). These findings were consistent across countries (pheterogeneity 0·10) and prespecified subgroups. In this large, international, real-world study of patients with type 2 diabetes, initiation of SGLT2 inhibitor therapy was associated with a slower rate of kidney function decline and lower risk of major kidney events compared with initiation of other glucose-lowering drugs. These data suggest that the benefits of SGLT2 inhibitors on kidney function identified in clinical trials seem to be largely generalisable to clinical practice. AstraZeneca.

Consistency of self-reported drug use events in a mixed methods study of people who inject drugs

Background: Little is known about the consistency of information provided by people who inject drugs (PWID) during quantitative and qualitative interviews in mixed methods studies.Objectives: We illustrate the use of the intraclass correlation coefficient, descriptive statistics, and regression to assess the consistency of information provided during a mixed methods study of PWID living in Los Angeles and San Francisco, California, USA. Methods: Age of first use of heroin, methamphetamine, marijuana, powder cocaine, and crack cocaine and first injection of heroin, methamphetamine, and powder cocaine were collected during an interviewer administered computer-assisted personal interview followed by an in-depth qualitative interview (n = 102). Results: Participants were 63% male, racially/ethnically diverse. 80.4% between the ages of 40 and 60 years old, 89% US-born, and 57% homeless. Consistency of self-reported data was adequate for most drug use events. Exact concordance between quantitative and qualitative measures of age of onset ranged from 18.2–50%. Event ordering was consistent across qualitative and quantitative results for 90.2% of participants. Analyses indicated that age of onset for heroin use, heroin injection, and injection of any drug was significantly lower when assessed by qualitative methods as compared to quantitative methods. Conclusion: While inconsistency will emerge during mixed method studies, confidence in the timing and ordering of major types of events such as drug initiation episodes appear to be warranted.

Holocene peatland initiation in the Greater Everglades

AbstractThe mechanisms involved in the initiation and development of the Greater Everglades peatland ecosystems remain a topic of discussion. In this study, we first present an overview of basal ages of peat deposits in South Florida, which shows two major episodes of peatland initiation between 7.0–4.5 kyr and 3.5–2.0 kyr. Our analysis of regional climate proxy data sets led to three alternative hypotheses that may explain the timing and duration of these two peatland initiation episodes: (1) decreased drainage due to relative sea level (RSL) rise during the Holocene, (2) gradual increase in precipitation throughout the Holocene, and (3) a combination of increasing precipitation, rising RSL, and oscillations in the climate system. We test whether these three hypotheses can explain the pattern of initiation and development of the Greater Everglades peatlands using models that simulate the nonlinear processes involved in peat production and decomposition. The model results suggest that RSL rise could explain the onset of peatland initiation and imply that the climate was wet enough for peat development also during the early Holocene. The first two hypothesized mechanisms in combination with climate oscillations may explain the onset of peat accumulation at 8.2 kyr B.P. The two‐phased character of peatland initiation maybe explained by the spatial distribution of local drainage conditions. As peatland development is highly nonlinear, our model uncovers a mechanistic way how peats can suddenly shift from a dry high equilibrium to a wet low equilibrium resulting in lake formation as observed in paleoecological studies in the Greater Everglades.

Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2 years of age

BackgroundEarly initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial...

Observations of Elevated Convection Initiation Leading to a Surface-Based Squall Line during 13 June IHOP_2002

AbstractThe evolution of a mesoscale convective system (MCS) observed during the International H2O Project that took place on the Great Plains of the United States is described. The MCS formed at night in a frontal zone, with four initiation episodes occurring between approximately 0000 and 0400 local time. Radar, radiosonde, and surface data together show that at least three of the initiation episodes were elevated, occurring from moist conditionally unstable layers located above the boundary layer, which had been stabilized by previous MCSs. Initiation occurred in northwest–southeast-oriented lines where a southerly nocturnal low-level jet terminated, generating elevated convergence. One initiation episode was observed using the S-band dual-polarization Doppler radar (S-Pol) and occurred at the intersection of this convergence zone with a propagating wave. Calculations of the Scorer parameter were consistent with wave trapping. Downdrafts from the developing convection generated both waves and bores, which propagated ahead of the cold pool, initiating further convection. Between 0700 and 1000 local time, the structure and orientation of the MCS evolved to a southwest–northeast-oriented squall line, which built a cold-pool outflow that could lift near-surface air to its level of free convection. The weaker cold pool in the eastern part of the domain was consistent with the greater impacts of a previous MCS there. To the authors’ knowledge, this case study provides the first detailed observational investigation of elevated initiation leading to surface-based convection, a process that appears to be an important mechanism for the generation of long-lived MCSs from elevated initiation.

The tuberculosis challenge in a rural South African HIV programme.

BackgroundSouth Africa remains the country with the greatest burden of HIV-infected individuals and the second highest estimated TB incidence per capita worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB incidence and an emerging epidemic of drug-resistant tuberculosis.MethodsReview of records of consecutive HIV-infected people initiated onto ART between 1st January 2005 and 31st March 2006. Patients were screened for TB at initiation and incident episodes recorded. CD4 counts, viral loads and follow-up status were recorded; data was censored on 5th August 2008. Geographic cluster analysis was performed using spatial scanning.Results801 patients were initiated. TB prevalence was 25.3%, associated with lower CD4 (AHR 2.61 p = 0.01 for CD4 <50 cells/μl) and prior TB (AHR 1.58 p = 0.02). Incidence was 6.89 per 100 person-years from 81 cases over 1175 person-years analysis time and was highest in the first 3 months after ART initiation; associated with male sex and higher log HIV RNA. Prevalent and incident TB were significantly associated with mortality (OR 1.81 p = 0.01 and 2.02 p = 0.01 respectively). Incident TB was associated with a non-significant trend towards viral load >25 copies/ml (OR 1.75 p = 0.11). A low-risk cluster for incident TB was identified for patients living near the local hospital in the geospatial analysis.ConclusionThere is a large burden of TB in this population. Rate of incident TB stabilises at a rate higher than that of the overall population. These data highlight the need for greater research on strategies for active case finding in rural settings and the need to focus on strengthening primary health care.

Mechanisms that initiate ventricular tachycardia in the infarcted human heart

BackgroundPrecise mechanisms that initiate ventricular tachycardia (VT) in the intact infarcted human heart have not been defined.ObjectiveThe purpose of this study was to investigate the mechanisms that underlie human postinfarct VT initiation.MethodsNoncontact mapping of the left ventricle was performed in 9 patients (age 67.1 ± 7.8 years, ejection fraction 34.4% ± 5%) with previous myocardial infarction and sustained monomorphic VT.ResultsCircuits in which ≥30% of the diastolic pathway (DP) could be defined were identified in 12 VTs (cycle length 357 ± 60 ms). Eighteen VT episodes were initiated with pacing, and one occurred spontaneously. Ten complete and two partial circuits were mapped (89% ± 25% of the DP). In all complete circuits, pacing led to the development of unidirectional conduction block at the location of the subsequent VT exit site and the formation of functional block creating a border(s) for subsequent DP. Wavefront velocity in the DP region slowed from 1.22 ± 0.2 m/s during sinus rhythm to 0.59 ± 0.14 m/s during VT (P <.005). In 11 initiation episodes, lines of functional block and areas of slow conduction developed progressively over one to six reentrant cycles before a stable DP was established and sustained monomorphic VT ensued. The formation of unidirectional or functional lines of block was not identified during identical pacing protocols that failed to initiate VT (n = 14).ConclusionInitiation of sustained monomorphic VT requires the development of unidirectional block and formation of lines of functional block creating borders for a DP in areas of slow conduction. A transitional stage often exists during the initiation process before a stable VT circuit is established.

Summary of Convective Storm Initiation and Evolution during IHOP: Observational and Modeling Perspective

Abstract The data-rich International H2O Project (IHOP_2002) experiment is used to study convective storm initiation and subsequent evolution for all days of the experiment. Initiation episodes were almost evenly divided between those triggered along surface-based convergence lines and elevated initiation episodes that showed no associated surface convergence. The elevated episodes occurred mostly at night, and the surface-based episodes occurred during the afternoon and evening. Surface-based initiations were mostly associated with synoptic fronts and gust fronts and less so with drylines and bores. Elevated initiations were frequently associated with observable convergent or confluent features in the Rapid Update Cycle (RUC) wind analysis fields between 900 and 600 hPa. The RUC10 3-h forecast of the precipitation initiation episodes were correct 44% of the time, allowing a tolerance of 250 km in space and for the forecast being early by one period. However, the accuracy was closely tied to the scale of the initiation mechanism, being highest for synoptic frontal features and lowest for gust fronts. Gust fronts were a primary feature influencing the evolution of the initiated storms. Almost one-half of the storm complexes associated with initiation episodes did not produce surface gust fronts. Storm systems that did not produce gust fronts most often lived 2–6 h while those that did frequently lived at least 8 h. The largest and longest-lived storm complexes had well-developed intense gust fronts that influenced the propagation of the storm system. The RUC10 was generally not successful in forecasting the evolution and motion of the larger, more intense storm complexes; presumably this was because it did not produce strong gust fronts. Implications for forecasting convective storm initiation and evolution are discussed.